Treatment Comparison in Rheumatoid Arthritis: Head-to-Head Trials and Innovative Study Designs

Abstract

Over the last decades, the increasing knowledge in the area of rheumatoid arthritis has progressively expanded the arsenal of available drugs, especially with the introduction of novel targeted therapies such as biological disease modifying antirheumatic drugs (DMARDs). In this situation, rheumatologists are offered a wide range of treatment options, but on the other side the need for comparisons between available drugs becomes more and more crucial in order to better define the strategies for the choice and the optimal sequencing. Indirect comparisons or meta-analyses of data coming from different randomised controlled trials (RCTs) are not immune to conceptual and technical challenges and often provide inconsistent results. In this review we examine some of the possible evolutions of traditional RCTs, such as the inclusion of active comparators, aimed at individualising treatments in real-life conditions. Although head-to-head RCTs may be considered the best tool to directly compare the efficacy and safety of two different DMARDs, surprisingly only 20 studies with such design have been published in the last 25 years. Given the recent advent of the first RCTs truly comparing biological DMARDs, we also review the state of the art of head-to-head trials in RA.

Factors influencing the choice of first- and second-line biologic therapy for the treatment of rheumatoid arthritis: real-life data from the Italian LORHEN Registry

“…Indeed, randomized controlled trials (RCTs), indirect comparison studies, meta-analysis, and head to head studies have failed to demonstrate a significant difference among the different classes of bDMARDs in terms of efficacy on clinical, functional, and radiographic outcomes [2][3][4][5]. The only exception being probably represented by TCZ monotherapy [6].…”

Heterogeneity in Comparisons of Discontinuation of Tumor Necrosis Factor Antagonists in Rheumatoid Arthritis - A Meta-Analysis

“…Evidence on the relative efficacy and safety of these medications is indirect and incomplete because no randomized controlled trials (RCTs) directly compare two or more TNF antagonists in RA patients [2]. Lack of efficacy and adverse effects are the most common reasons for discontinuing TNF antagonists [3–9], and therefore discontinuation risk is a good measure of the benefit-harm balance of these medications [10].…”

Efficacy and safety of tofacitinib for immune-mediated inflammatory rheumatic diseases (Part I)

“…РБ -рекомбинантные белки; TRAF2 -TNF receptor-associated factor 2; PI3K -phosphoinositide-3-kinase-protein kinase B/Akt; C/EBPβ -CCAAT/enhancerbinding protein beta; NF-κB -nuclear factor kappa -light-chain-enhancer of activated B cells; MyD88 -Myeloid differentiation primary response gene 88; MAPK -mitogenactivated protein kinase; IRAK1 -interleukin-1 receptor-associated kinase; CXCR -C-X-C chemokine receptor; CXCL -C-X-C chemokine ligand. П р о г р е с с в р е в м а т о л о г и и в X X I в е к е Открытые исследования и регистры РПКИ занимают центральное место в медицине, основанной на доказательствах [96][97][98], однако использование «жестких» критериев «включения» и «исключения» затрудняет генерализацию полученных данных на всю популяцию пациентов, наблюдаемых в клинической практике. Эта проблема получила название «брешь эффективностирезультативности» (efficacy-effectiveness gap) [99], которая в определенной степени может быть преодолена материалами регистров пациентов, позволяющими составить более полное представление об истинном месте лекарственных препаратов [100][101][102][103][104], включая ТОФА [105], в реальной клинической практике.…”